Apparatus and method for blocking activation of tissue or conduction of action potentials while other tissue is being therapeutically activated

ABSTRACT

A desired effect is produced by therapeutically activating tissue at a first site within a patient&#39;s body and a corresponding undesired side effect is reduced by blocking activation of tissue or conduction of action potentials at a second site within the patient&#39;s body by applying high frequency stimulation and/or direct current pulses at or near the second site. Time-varying DC pulses may be used before or after a high frequency blocking signal. The high frequency stimulation may begin before and continue during the therapeutic activation. The high frequency stimulation may begin with a relatively low amplitude, and the amplitude may be gradually increased. The desired effect may be promotion of micturition or defecation and the undesired side effect may be sphincter contraction. The desired effect may be defibrillation of the patient&#39;s atria or defibrillation of the patient&#39;s ventricles, and the undesired side effect may be pain.

FIELD OF THE INVENTION

[0001] This invention relates to techniques for blocking activation ofelectrically excitable tissue within a patient's body, and moreparticularly relates to techniques for producing a desired effect bytherapeutically activating tissue at a first predetermined site within apatient's body and for reducing a corresponding undesired side effect byblocking activation of tissue at a second predetermined site within thepatient's body.

DESCRIPTION OF RELATED ART

[0002] It is often desirable to therapeutically activate excitabletissue, such as nerve, muscle, or glandular cells of a patient byelectrical stimulation or via medications. An undesirable side effect ofsuch therapeutic activation of excitable tissue is that other tissue,either nearby or distant, may be undesirably activated, either directlyby the same mode of activation, or indirectly by sensory feedback orother reflexes.

[0003] Generally, undesired action potentials in sensory nerves ordorsal roots may either be disagreeable to the patient or cause contraryeffects. When stimulating to assist peristalsis in the esophagus,ureter, stomach, or intestine, co-contraction of sphincters ordisagreeable sensations or reverse peristalsis might be undesirable. Forinstance, if a patient is unable to control urination or defecation,stimulation of peripheral nerves or ventral roots to contract apatient's bladder for micturition or to move bowel contents may bedesirable. Such activation, or even lower amplitude stimulation,however, will typically create action potentials in sphincters, such asthose in the external urethra or anus. Such action potentials will tendto cause the sphincters to contract, which may result in an inability topass urine or fecal matter beyond the sphincters. In addition, increasedpressure in the bladder caused by simultaneous compression of thepatient's bladder and contraction of the patient's external urethralsphincter may lead to injury to the patient, including increasedpressure and damage to either or both the bladder and the kidneys. Aconventional approach that has been proposed for patients that aresubstantially paralyzed is to cut the patient's nerves that lead backinto the spinal cord (dorsal roots) so that the stimulation of thebladder does not cause a lot of neural activity in the spinal cord. If apatient's bladder is significantly overfilled, autonomic dysreflexia mayoccur causing a very large and dangerous increase in the patient's bloodpressure, which may cause a stroke.

[0004] When stimulating to defibrillate a patient's heart, extremelyintense pain is typically inflicted upon the patient due to simultaneousactivation of many afferent fibers, some of which may even be the axonsof nociceptors.

[0005] When stimulating certain motorneurons, activations directly or byspinal reflex of antagonistic motorneurons and muscles may interferewith the desired motion, necessitating an increase in the strength ofstimulation, which causes increased rigidity of a patient's joints.

[0006] Electrical excitation of tissue at low frequencies (e.g., lessthan 100 Hertz) has been known to cause action potentials in nerve andmuscle. In addition, some techniques have been described to block actionpotentials in certain nerve fibers, with the best observations done inanimal experiments.

[0007] Tanner (Nature, vol. 195, 1962: 712-713) and Woo & Campbell(Bull. L.A. Neurol. Soc., vol. 29, 1964:87-94) showed that 20,000 Hzstimulation of a nerve is able to block passing action potentials, withlarger voltages (amplitudes) needed to progressively block smallerfibers. Recently, from therapeutic stimulation of the brain in patientswith tremor and other symptoms of Parkinson's disease, evidence hasmounted that high frequency stimulation (100-185 Hertz) keeps neuronsdepolarized, and hence incapable of producing action potentials (Benabidet al., Lancet, vol. 337, 1991: 403-406; Benazzouz et al., Neurosci.Lett., vol. 189, 1995: 7780). High frequency stimulation of the spinalcord or nerves (250 Hertz and more) has been anecdotally reported torelieve chronic pain, but whether this works by blocking of actionpotentials is unknown (Picaza et al., Surg. Neurol., vol. 4, 1975:105-114 and 115-126; Sheldon et al., Surg. Neurol., vol. 4, 1975:127-132; Bennett et al., Neuromodulation, vol. 2, 1999: 202-210).

[0008] Mendel & Wall (J. Physiol., vol. 172, 1964: 274-294) and Campbell& Woo (Bull. Los Angeles Neurol. Soc., vol. 31, 1966: 63-71)demonstrated a similar amplitude-dependent blocking of action potentialsin progressively smaller axons using direct current (D.C.) signals.Recently, evidence has developed that repetitive stimulation in rats ofthe brain area called the amygdala, which can cause seizures due tokindling, can have its kindling effects quenched by use of 5 to 15microampere D.C. currents applied once a day for 15 minutes (Weiss etal., Exper. Neurol., vol. 154, 1998: 185-192).

[0009] The disadvantage of direct current pulses is that they can leadto tissue or electrode damage (Pudenz, et al, Surg. Neurol., vol. 4,1975:265-270) or to asynchronous repetitive action potential discharges(Manfredi, Arch. Ital. Biol., vol 108, 1970: 52-71; Sassen & Zimmerman,Pflugers Arch. Gesamte Physiol. Menschen Tiere, vol. 341, 1973:179-195).

[0010] Van den Honert & Mortimer (IEEE trans. BME., vol. 28, 1981:373-378 and 379-382) developed a technique to create action potentialsthat propagate in only one direction along axons using a tripolar cuffwith three electrodes and two regulated current stimulators. This methodwas used by Brindley & Craggs (J. Neurol. Neurosurg. Psychiat., vol. 43,1980: 1083-1090) to excite only the smaller (parasympathetic) fibers inspinal nerve roots and peripheral nerves for bladder emptying. Ungar,Mortimer & Sweeney (Ann. Biomed. Engng, vol. 14, 1986: 437-450) werealso able to generate unidirectionally propagating action potentials innerves using an asymmetric monopolar electrode cuff. However, both ofthese partial-blocking techniques require complete encirclement of theaxons of interest with non-conducting materials, something which thehigh frequency and D.C. techniques do not require.

[0011] In order to minimize undesirable side effects associated withtherapeutic activation of tissue, including, but not limited to, theside effects mentioned above, it may be desirable to deactivate orinhibit certain excitable tissue during the time that the desired effectis being produced in the therapeutically activated tissue.

[0012] It would, therefore, be desirable to block action potentials intissue that are deliberately generated from low frequency stimulation.The block may not be complete, and there may be asynchronous, evenrepetitive generation of some action potentials in the process, butunder certain circumstances, it may be possible to prevent most of theaction potentials in certain nerves that otherwise may be caused byother electrodes in nearby tissue that use deliberate low frequencypulses to cause action potentials. The volume of tissue recruited nearthe deliberate “activation” electrodes and the volume of tissueinhibited near the “blocking” electrodes would both depend upon theparameters of stimulation, especially the amplitude and pulse width.

SUMMARY OF THE INVENTION

[0013] In accordance with certain inventive principles, a desired effectis produced by therapeutically activating tissue at a first site withina patient's body and a corresponding undesired side effect is reduced byblocking activation of tissue at a second site within the patient's bodyby applying high frequency stimulation and/or one or more direct currentpulses at or near the second site.

[0014] In accordance with various inventive principles, the desiredeffect may be promotion of micturition; the undesired side effect may besphincter contraction; the first site may be the patient's bladder dome,sacral roots, or pelvic plexus; and the second site may be thepatient's: sacral dorsal roots, spinal dorsal columns, conus medullaris,pudendal nerve, hypogastric plexi, or perineal nerve.

[0015] The desired effect may be promotion of defecation; the undesiredside effect may be sphincter contraction, elevated pelvic floor, orsharp ano-rectal angle; the first site may be the patient's: hypogastricplexus, pelvic plexus, nerves to rectum, sacral roots, pelvic plexus, orrectal muscle; and the second site may be the patient's: sacral dorsalroots, spinal dorsal columns, conus medullaris, pudendal nerve, ornerves to the patient's pelvic floor muscles.

[0016] The desired effect may be peristalsis of the patient's esophagus;the undesired side effect may be contraction at the patient'sgastroesphageal sphincter; the first site may be the patient's:esophagus, nerves to the patient's esophagus, pharynx, or nerves to thepatient's pharynx; and the second site may be the patient's: hiatalesophagus area near the patient's diaphragm, or nerves to the patient'sesophagus.

[0017] The desired effect may be peristalsis of the patient's ureter;the undesired side effect may be closure of the patient's anti-refluxvalves near the patient's bladder trigone; the first site may be thepatient's: renal pelvis or a portion of the patient's ureter; and thesecond site may be the patient's: base of the bladder near an entranceof a ureter, hypogastric plexus, or pelvic plexus.

[0018] The desired effect may be peristalsis of the patient's stomach;the undesired effect may be closure of the patient's pyloric sphincter;the first site may be the patient's: stomach wall muscles or the nervesleading to the patient's stomach wall muscles; and the second site maybe the patient's: muscle fibers of the pyloric sphincter or nerves tothe pyloric sphincter.

[0019] The desired effect may be peristalsis of the patient's intestine;the undesired effect may be closure of the patient's ileocecal valve tothe patient's colon; the first site may be the patient's: intestinalwall smooth muscle, hypogastric plexus, or nerves to the patient'shypogastric plexus; and the second site may be the patient's: ileocecalvalve, mesenteric ganglia, dorsal root, spinal dorsal columns, orsplanchnic nerves.

[0020] The desired effect may be selected from the group consisting of:defibrillation of the patient's atria or defibrillation of the patient'sventricles; the undesired side effect may be pain; the first site may benear a heart pacing/defibrillation lead: inside the patient's heartchambers or outside the patient's heart chambers; the second site may bethe patient's: vagus nerve, branches of the patient's vagus nerve fromthe patient's heart, thoracic sympathetic nerves, ansa subclavia,sympathetic trunk ganglia (T1-T4), stellate ganglia, cervical ganglia(C1-C8), celiac plexus, brachial plexi, dorsal roots (C1-T4), spinaldorsal columns, or dorsal roots.

[0021] The desired effect may be extension of the patient's leg; theundesired side effect may be co-contraction of the antagonist muscles;the first site may be the patient's femoral nerve to the patient'squadriceps femoris; and the second site may be the patient's tibialnerve to the patient's gastrocnemius muscle.

[0022] The desired effect may be movement of one of the patient's jointsin a predetermined direction; the undesired side effect may beco-contraction of antagonist muscles; the first site may be thepatient's peripheral nerve; and the second site may be the patient'snerve branch to an antagonist muscle.

[0023] The high frequency blocking stimulation may begin before andcontinue during the therapeutic activation. The high frequency blockingstimulation may begin with a relatively low amplitude, and the amplitudemay be gradually increased. The high frequency blocking stimulation maybe terminated by gradually reducing the amplitude of the high frequencystimulation.

[0024] A sensor may be included for sensing a state of the tissue at thesecond site or at a more remote site. Means, responsive to the sensor,for adjusting the pulse amplitude, pulse width, pulse frequency, pulseduty cycle, pulse polarity, or pulse waveform of the high frequencyblocking stimulation at the second site may also be included.

[0025] Direct current pulses may be used to block activation of thetissue at the second site. If ramped up or down gradually, this mayallow neuronal accommodation and prevent action potentials. Directcurrent pulses may also be used before or after a series of highfrequency blocking signals, so that much of the stimulation for blockinghas charge balance to protect the electrodes or tissue.

BRIEF DESCRIPTION OF THE DRAWINGS

[0026]FIG. 1 is a diagrammatic illustration of a system for blockingactivation of tissue within a patient according to various inventiveprinciples.

[0027]FIG. 2 shows blocking stimulation starting before and ending afterintended effect stimulation.

[0028]FIGS. 3a-3 d show various combinations and permutations of highfrequency and/or direct current blocking pulses with and/or withoutramping at the beginning and/or end of the pulses.

[0029]FIG. 4 is a flow chart depicting steps that may be performed toblock activation of tissue in accordance with certain inventiveprinciples.

[0030]FIG. 5 is a schematic diagram showing electrode placement forpromotion of micturition in accordance with various inventiveprinciples.

[0031]FIG. 6 is a schematic diagram showing electrode placement in apatient's intrathecal space near the patient's dorsal root for blockingsensations associated with stimulation of another part of the patient'sbody.

[0032]FIG. 7 is a schematic diagram showing electrode placement forassisting peristalsis of a patient's esophagus and/or emptying thepatient's stomach.

[0033]FIG. 8 is a schematic diagram showing electrode placement forextending a patient's lower leg.

[0034]FIG. 9 is a schematic diagram showing electrode placement forpromotion of defecation in accordance with various inventive principles.

[0035]FIG. 10 is a schematic diagram showing suitable electrodeplacement for reducing pain perceived by a patient associated withdefibrillation pulses.

DETAILED DESCRIPTION OF THE INVENTION

[0036] Evidence, from stimulation of the brain for tremor and othersymptoms of Parkinson's disease, indicates that high frequencystimulation keeps neurons depolarized, and hence incapable of causing anaction potential. See A. L. Benabid et al., Long-Term Suppression ofTremor by Chronic Stimulation of the Ventral Intermediate ThalamicNucleus, the Lancet, vol. 337, 1991, pp. 403-406. Accordingly, thetherapies of deep brain stimulation to block tremor and to blockneuronal pathways that prevent desired volitional movements (freezing,akinesia, bradykinesia) often use high frequency stimulation. Forinstance, commonly assigned U.S. Pat. Nos. 5,716,377 and 5,833,709disclose such systems and methods and are incorporated herein byreference. As used herein, the phrase “high frequency stimulation”refers to electrical stimulation of at least approximately 100-120 Hz,while “low frequency stimulation” refers to electrical stimulation ofless than approximately 100 Hz.

[0037]FIG. 1 is a schematic view of a patient 110 having an implant of aneurological stimulation system employing a preferred form of thepresent invention. A system in accordance with the principles of theinvention may employ an implantable pulse generator 114 to producestimulation pulses to various predetermined sites within a patient'sbody. For instance, as depicted in FIG. 1, the concept of applying highfrequency blocking stimulation with electrode 140 is depictedschematically. High frequency stimulation is applied in order to preventan undesirable side effect of spinal cord stimulation applied viaelectrode 118. In accordance with the principles of this invention, thesite at which an undesirable side effect is blocked using high frequencystimulation will often be located in close proximity to the locationwithin the patient's body at which low frequency intended effectstimulation is applied. Nevertheless, the two types of stimulation maybe applied in areas of a patient's body that are relatively far apart,as shown, for instance, in FIG. 1. Another example is applying highfrequency blocking stimulation to block pain perceived by a patientwhile administering a defibrillation pulse to the patient's heart, theblocking stimulation may be applied in locations away from the heart, asdescribed in more detail below.

[0038] In a preferred embodiment, implantable signal generator 114 maybe a modified signal generator, such as Model 7424 manufactured byMedtronic, Inc. under the trademark Itrel®, or pulse generator 114 mightnot have a battery and might instead get programming signals and energyfrom a modified exterior transmitter 120 and antenna 124 like a radiofrequency system manufactured by Medtronic, Inc. known as X-trel® orMattrix®. Signal generator 114 could simultaneously produce both highand low frequency stimulation, for instance, at frequencies above andbelow 100 Hz, respectively. Alternatively, signal generator 114 couldoutput either high or low frequency stimulation and a second signalgenerator, not shown, could be used to output the other type ofstimulation.

[0039] For spinal cord stimulation (SCS), signal generator 114 iscommonly implanted subcutaneously in a human body in the abdomen orback. In accordance with the principles of this invention, one or moresignal generators may be placed near a location that will betherapeutically activated or near an area in which activation willblocked or near both such types of areas. Electrodes 140 and 118 may beoperatively coupled to signal generator 114 by leads 115 and 116,respectively. Alternatively, Electrodes 140 and 118 may be operativelycoupled to signal generator 114 by a single lead.

[0040]FIG. 2 depicts high frequency blocking stimulation beginningearlier in time than the intended effect stimulation and continuinguntil after the intended effect stimulation has finished. By startingthe high frequency blocking stimulation before and continuing it afterthe intended effect stimulation is applied, undesirable side effectsassociated with the intended effect stimulation may be blocked moreeffectively than would be possible if the high frequency blockingstimulation did not start until the same time as, or after, and/orstopped at the same time, or before, the intended effect stimulation.The intended effect stimulation may be a single pulse or multiplepulses.

[0041] The waveform at the top of FIG. 3a depicts high frequencyblocking stimulation pulses that start and stop without any ramping orgradual increase or decrease of the amplitude of the pulses. The middleand lower waveforms, depict blocking pulse waveforms in which theamplitude of the waveform is ramped up or gradually increased at thebeginning of the waveform, and ramped down or gradually decreased at theend of the waveform, respectively. Such ramping may be used in order tominimize creation of any action potentials that may be caused by moreabruptly starting and/or more abruptly stopping the high frequencyblocking stimulation.

[0042] Creation of a blocking signal without action potentials beingcaused by the high frequency blocking pulses is desirable. As shown inFIG. 3b, a straight direct current pulse may be employed throughout thetime for blocking. It may be depolarizing, especially if it has agradual ramp that allows accommodation of the neural tissue to preventaction potentials from developing. Action potentials that approach theregion run into areas where neuronal sodium gates are already affectedand thus cannot open. It may also be of opposite sign, hyperpolarizing.This prevents action potentials from starting when the transmembranepotential cannot be sufficiently reduced to open the sodium channels,but action potentials approaching the region might still pass through.

[0043] A danger associated with direct current pulses is that there maybe electrode dissolution and neuronal damage due to a steady and longdistance flow of ions. However, such stimulation may be appliedrelatively infrequently, for instance just a few times per hour or permonth, depending on the application. The ability to shield the sideeffects, therefore, may outweigh the dangers from intermittent directcurrent stimulation.

[0044]FIG. 3c shows a combination of modes for blocking. There is agradual DC ramp and then a series of high frequency pulses. The ramp mayproduce accommodation of neurons, and prevent any action potentials. Thecontinuation of high frequency stimulation may keep neurons deactivated,while still producing charge-balanced pulses. This technique may be usedto advantage to prevent initial action potentials and to minimizeelectrode or tissue problems.

[0045]FIG. 3d shows multiple combinations with a variety of DC pulses.The initial pulse might have an exponential rise instead of a linearrise. The end of the blocking signal might also use a DC pulse to allowthe neuronal tissue to return to its excitable state without causingactivations, for example, anodal break.

[0046]FIG. 4 is a flow chart depicting steps that may be performed toblock activation of tissue in accordance with certain inventiveprinciples. At step 402, high frequency blocking stimulation is startedand may optionally be ramped as described above with reference to FIG.3. At step 404, low frequency intended effect stimulation is started. Atstep 406, a determination may be made as to how effectively the highfrequency stimulation is blocking one or more undesirable side effectsassociated with the intended effect stimulation. This determination maybe performed by a suitable sensor for measuring various parameters, suchas movement of limb, contraction of sphincter, or any other suitablemeasurement indicating the degree to which an undesired side effect hasbeen blocked.

[0047] If the blocking stimulation is determined to be insufficient, adetermination is made as to whether a predetermined limit on the amountof blocking stimulation to be applied has been reached, as shown at 408and 410. If the blocking stimulation limitation has not yet beenreached, the blocking stimulation may be increased at step 402, the lowfrequency stimulation may be continued as shown in step 404, and thedeterminations may be made again as shown at 408 and 410.

[0048] If the blocking stimulation is determined to be sufficient, theintended effect, also referred to as target tissue, stimulation may becontinued for as long as is desirable, as shown at 408 and 412. Afterterminating the intended effect stimulation at 412, the high frequencyblocking stimulation may be terminated, as shown at 414.

[0049] Turning now to example applications of the principles of thisinvention, FIG. 5 is a schematic diagram showing electrode placement forpromotion of micturition in accordance with various inventiveprinciples. Anterior sacral root 513 is shown originating from spinalcord 512, which is shown in a sectional view. Electrode 515 is shown inclose proximity to anterior sacral root (S1-S4) 513. Low frequencyintended effect stimulation may be applied to sacral root 513 viaelectrode 515 in order to promote micturition by causing actionpotentials in nerve 507 leading to bladder 510. In order to blockactivation of external sphincter 508 of the urethra in the pelvic floormuscles of a patient, high frequency blocking stimulation may be appliednear branch 509 of pudendal nerve leading to external sphincter 508. Thehigh frequency blocking stimulation is preferably started before andcontinued after the application of the low frequency intended effectstimulation. In addition to the sacral roots, low frequency intendedeffect stimulation may also be applied to other parts of the patient'sbody, including, but not limited to, the patient's bladder dome and/orthe patient's pelvic plexis of nerves. Sphincter contraction may also beprevented by application of high frequency blocking stimulation atlocations other than the patient's pudendal nerve, including, but notlimited to, the patient's sacral dorsal roots, spinal dorsal columns,conus medullaris, hypogastric plexus, and perineal nerve.

[0050]FIG. 6 is a schematic diagram showing placement of electrode 614in a patient's intrathecal space near the patient's dorsal root forblocking sensations associated with stimulation of another part of thepatient's body. As discussed in the Background of the Invention sectionabove, stimulating nerves leading to bladder 510, without blockingactivation of the external sphincter 508, may lead to reflex sympatheticdystrophy and stroke, among other complications. Rather than cut theafferent nerves, as has been proposed in U.S. patents to Tanagho andSchmidt et al. U.S. Pat. Nos. 4,607,639; 4,703,755; and 4,771,779)*, thedorsal roots may be stimulated at high frequency to block theiractivation while the bladder is contracting, thereby reversibly blockingactivation of the dorsal root tissue, as shown in FIG. 6. In addition topreventing reflex sympathetic dystrophy, application of high frequencystimulation via lead 616 may prevent undesirable sensation associatedwith the low frequency stimulation applied to contract the patient'sbladder by preventing activation of the patient's dorsal root. As willbe apparent, undesirable sensations from many sources other than thepatient's bladder may also be blocked in a similar manner. As will alsobe apparent, electrode 614 may also be placed in other suitable areas inorder to block activation of other tissue thereby preventing otherundesirable effects of low frequency intended effect stimulation appliedelsewhere in a patient's body. For instance, electrode 614 may be placedoutside the arachnoid membrane 660 in the subdural space 654 or outsidedura 652 in the epidural space 670.

[0051] Blocking signals can be delivered at any of these sites to notonly prevent pain, but also prevent nerve action potentials fromentering the spinal cord and causing undesired reflexes. If pain is thechief undesired side effect from nerve or tissue activation, then it ispossible to block it as it ascends the spinal cord near the surface ofthe ventrolateral quadrant, in the spinothalamic tract, on the oppositeside of the spinal cord, since pain fibers cross near their point oforigin. It may be advantageous to place an electrode under the dura,next to the pial surface in this case, to not also cause loss ofsensations or motor control on that opposite side.

[0052]FIG. 7 is a schematic diagram showing electrode placement forassisting peristalsis of a patient's esophagus and/or emptying thepatient's stomach. Branches of vagus nerve 46 are shown along esophagus38 and stomach 35 and connecting to myenteric nervous system 44, whichare local neurons involved in peristaltic contraction of the esophagus.High frequency blocking stimulation may be applied via electrode 32 nearthe hiatal portion of the esophagus, which is where the bottom portionof the esophagus 38 meets upper portion of stomach 35. Low frequencyintended effect stimulation may then be applied by upper electrode 31 topromote peristalsis of the esophagus in order to move food down theesophagus and into the stomach. The high frequency blocking stimulationwill prevent the low frequency intended effect stimulation fromundesirably causing the hiatal portion of the esophagus to contract.Peristalsis of the patient's esophagus may also be promoted byapplication of low frequency intended effect stimulation of thepatient's pharynx. Contraction of the patient's gastroesphagealsphincter may be prevented by application of high frequency blockingstimulation to nerves leading to that portion of the patient'sesophagus.

[0053] In a similar manner, contraction of pyloric sphincter 37 may beprevented by applying high frequency stimulation via electrode 39 whileapplying low frequency stimulation to the stomach muscle 35 or toelectrodes 33 and 34 located in close proximity to descending branchesof celiac ganglia 40 in order to move food from the patient's stomach 35to the patient's intestine 36.

[0054] Peristalsis of the ureter, to move urine to the bladder, and theintestine, to move food materials along, are also normal physiologicalfunctions of the urinary and digestion system that may becomecompromised by trauma or disease. Although not depicted in FIG. 7, inthese cases, there could be activation at low frequency to start theperistalsis of material. In the case of the ureter, the activationshould be in the renal pelvis portion of the kidney, or near the top ofthe ureter, above any segment that is paralyzed, or at intact nervesgoing to those structures. In the case of the intestine, activationshould be anywhere along the intestine that there is a functionalproblem, or at intact nerves going to that portion of bowel. Activationmay have to be done in a delayed, sequential process along the length ofthe structure as well, to keep the peristalsis moving adequately.Blocking of excitation using high frequency stimulation and/or directcurrent potentials should be done where a particular valve may not befunctionally opening as required. In the case of the ureter, this mightbe near the bladder's trigone, where an anti-reflux valve usually helpsprevent urine flow back toward the kidney, or at intact nerves thatinnervate that portion of the bladder. In the case of the intestine,this might be at the ileocecal valve, or at nerves that go to that areaof the intestine. In cases where peristalsis can be restored by lowfrequency activation and there is undesirable sensation being produced,blocking can be done on the dorsal columns or dorsal roots of sensorysignals going to the spinal cord and brain. It is conceivable thatblocking of tissue excitation should be done in two locations: at anonfunctioning valve, to prevent excitation by the peristaltic wave,done at an appropriate time related to the speed of peristalsis anddistances, and at the spinal sensory pathways, to prevent passage ofaction potentials, mostly useful near the time the desired peristalsisis begun by low frequency activation.

[0055] Referring to FIG. 8, electrode placement is depicted forfunctional electrical stimulation to control muscles for extending apatient's leg. Nerve 54, leading to muscle 50, may be stimulated byelectrode 56 causing muscle 50 to contract such that the patient's tibia52 will move in the direction of arrow 58, thereby straightening thepatient's leg. Such stimulation may undesirably cause simultaneouscontraction of an antagonist muscle, such as muscle 51. Therefore, nerve55 may be stimulated with high frequency blocking stimulation atelectrode 57 to prevent action potentials in nerve 55 from causingcontraction of muscle 51. As will be apparent, applying varying levelsof high frequency stimulation to muscle 51 may be desirable in order tomove tibia 52 in a controlled fashion. The amount and/or duration ofeither or both types of stimulation may be controlled as described abovein connection with FIG. 4. For example, when a person is standing up,tension in both muscles is desirable. Low frequency stimulation fromelectrode 56 may be applied to both nerves 54 and 55, while highfrequency stimulation may be applied to modulate the action potentialsthat can get through to muscle 51, thereby reducing the amount of axonsin nerve 55 that cause contraction of muscle 51.

[0056]FIG. 9 is a schematic diagram showing electrode placement forpromotion of defecation in accordance with various inventive principles.Nerves 75 outside descending colon 70 and nerve plexus 76 in the wall ofrectum 71 are shown. Low frequency stimulation in the area of pelvicplexus nerves to rectum 77, which could be used to contract the rectumto promote defecation, may also stimulate pudendal nerve 78, directly,or by reflex arc, in a similar manner as described above with respect tothe bladder and FIG. 5. Accordingly, high frequency blocking stimulationmay be applied via electrode 79 to pudendal nerve 78 to prevent actionpotentials in pudendal nerve 78, which would undesirably cause pelvicfloor muscles or anal sphincter muscles 72 to contract. Pelvic plexusnerves 77 originate from the sacral roots as does the pudendal nerve 78.Using low frequency sacral root stimulation, pudendal nerve 78 will beactivated at a lower amplitude than pelvic plexus nerves 77 becausepudendal nerve 78 contains larger diameter axons. At higher amplitudesof low frequency stimulation the rectum may contract, but the pudendalnerve 78 will be activated and will prevent defecation. This phenomenonalso applies to stimulation of the nerves discussed with respect to thebladder. Accordingly, the bladder and the rectum cannot be contractedwith low frequency stimulation until its sphincter has already beenundesirably contracted, absent high frequency blocking stimulationapplied to a nerve leading to the sphincter. To promote defecation, lowfrequency intended effect stimulation may also be applied at other areasin a patient's body, including, but not limited to, the patient'shypogastric plexus, pelvic plexus, nerves along the patient's rectum,and sacral roots. Undesired side effects of such low frequency intendedeffect stimulation, may include, but are not limited to, sphinctercontraction, elevation of the pelvic floor, and promotion of a sharpano-rectal angle. These can be prevented by application of highfrequency or direct current blocking stimulation to other part or thepatient's body, including, but not limited to, the patient's sacraldorsal roots, spinal dorsal columns, conus medullaris, and nerves to thepatient's pelvic floor muscles.

[0057] As mentioned above, defibrillation of a patient's heart by use ofstrong electric pulses is extremely painful. Commonly assigned U.S. Pat.No. 5,817,131, which issued to Elsberry et al. and is incorporatedherein by reference, discloses blocking of pain messages using spinalcord stimulation or stimulation in other sites in peripheral or centralpathways. The Elsberry '131 patent discloses blocking of pain messagesvia the Gate Control Hypothesis, which involves stimulation typically ata frequency below 100 Hz near the doral columns. Presumably, largerdiameter fibers are stimulated to block the smaller diameter fibers,which carry pain and temperature. In accordance with the principles ofthe instant invention, high frequency stimulation, in other words,stimulation at frequencies above 100 Hz, may be used to blocksubstantially all afferent nerves near the heart, including the smalldiameter fibers which often carry pain messages. High frequency ordirect current blocking stimulation may preferably be applied toperipheral nerves, including nerves from the heart, such as vagus orsympathetic nerves or both, which tend to have small diameter axons.

[0058]FIG. 10 is a schematic diagram showing suitable electrodeplacement for reducing pain perceived by a patient associated withdefibrillation pulses. Pain information may travel from the heart bygoing to the left in FIG. 10 through the parasympathetic vagus nerve 81due to its branches, 82-84. Pain information may also travel from theheart to the right in FIG. 10 into the sympathetic system via nervesexiting the heart 91. These nerves bring information, especially aboutpain, to the stellate sympathetic ganglia 85 or to the T1-T4 thoracicganglia 86, 88, 89, and 90. In order to block pain signals insympathetic efferent nerves 91, electrodes could be placed near thosenerves either before, 93 and 100, or after, 94 and 99, they pass to thesympathetic ganglia 85, 86, 88, 89, and 90. These electrodes may beplaced endoscopically using a needle near the branches of these nerves.While defibrillating a patient's atria or ventricles, low frequencyintended effect stimulation may be applied via a heartpacing/defibrillation lead inside the patient's heart chambers or via aheart pacing/defibrillation lead outside the patient's heart chambers.Pain associated with defibrillating a patient's atria or ventricles maybe prevented by application of high frequency or direct current blockingstimulation to locations within the patient's body including, but notlimited to, the bilateral vagus nerves, branches of the patient's vagusnerves near the patient's heart, sympathetic nerves near the heart, ansasubclavia, sympathetic trunk ganglia (T1-T4), stellate ganglia, cervicalganglia, celiac plexus, brachial plexi, dorsal columns and dorsal roots(C1-T4).

[0059] If the ventricles are being defibrillated, blocking stimulationmay be applied to lower ganglia 89 and 90 via electrode 93, for example.Atrial defibrillation, on the other hand, will typically be needed moreoften, for instance many times per day. High frequency stimulation maybe applied to electrodes 94, 99 or 100 for the upper sympathetic ganglia85, 86, 88 and electrode 96, 97 or 98 may be used for blocking paininformation transmitted via the vagus nerve, depending upon wheredefibrillation occurs.

[0060] The preferred embodiments may be altered or amended withoutdeparting from the true spirit and scope of the invention, as defined inthe accompanying claims.

I claim:
 1. A system for producing a desired effect by therapeuticallyactivating tissue at a first predetermined site within a patient's bodyand for reducing a corresponding undesired side effect by blockingactivation of tissue or conduction of action potentials at a secondpredetermined site within the patient's body, the system comprising: afirst signal generator for producing low frequency stimulation; a secondsignal generator for producing high frequency and/or direct currentpulse stimulation; and at least one implantable lead including a firstelectrode coupled to the first signal generator, the first electrodebeing adapted to therapeutically activate tissue at the firstpredetermined site by applying low frequency stimulation, the at leastone implantable lead including a second electrode coupled to the secondsignal generator, the second electrode being adapted to block activationof electrically excitable tissue at the second site by applying highfrequency stimulation or one or more direct current pulses or both highfrequency stimulation and one or more direct current pulses at or nearthe second site.
 2. The system of claim 1, wherein: the desired effectis promotion of micturition; and the undesired side effect is sphinctercontraction.
 3. The system of claim 2, wherein: the first site isselected from the group consisting of the patient's bladder dome, sacralroots, and pelvic plexus.
 4. The system of claim 3, wherein: the secondsite is selected from the group consisting of the patient's: sacraldorsal roots, spinal dorsal columns, conus medullaris, pudendal nerve,hypogastric plexi, and perineal nerve.
 5. The system of claim 1,wherein: the desired effect is promotion of defecation; and theundesired side effect is selected from the group consisting of:sphincter contraction, elevated pelvic floor, and sharp ano-rectalangle.
 6. The system of claim 5, wherein: the first site is selectedfrom the group consisting of the patient's: hypogastric plexus, pelvicplexus, nerves to rectum, sacral roots, pelvic plexus, and rectalmuscle.
 7. The system of claim 5, wherein: the second site is selectedfrom the group consisting of the patient's: sacral dorsal roots, spinaldorsal columns, conus medullaris, pudendal nerve, and nerves to thepatient's pelvic floor muscles.
 8. The system of claim 1, wherein: thedesired effect is peristalsis of the patient's esophagus; and theundesired side effect is contraction at the patient's gastroesphagealsphincter.
 9. The system of claim 8, wherein: the first site is selectedfrom the group consisting of the patient's: esophagus, nerves to thepatient's esophagus, pharynx, and nerves to the patient's pharynx. 10.The system of claim 8, wherein: the second site is selected from thegroup consisting of the patient's: hiatal esophagus area near thepatient's diaphragm and nerves to the patient's esophagus.
 11. Thesystem of claim 1, wherein: the desired effect is peristalsis of thepatient's ureter; and the undesired side effect is closure of thepatient's anti-reflux valves near the patient's bladder trigone.
 12. Thesystem of claim 10, wherein: the first site is selected from the groupconsisting of the patient's: renal pelvis and a portion of the patient'sureter.
 13. The system of claim 10, wherein: the second site is selectedfrom the group consisting of the patient's: base of the bladder near anentrance of the ureter, hypogastric plexus, and pelvic plexus.
 14. Thesystem of claim 1, wherein: the desired effect is peristalsis of thepatient's stomach; and the undesired effect is closure of the patient'spyloric sphincter.
 15. The system of claim 14, wherein: the first siteis selected from the group consisting of the patient's: stomach wallmuscles and nerves leading to the patient's stomach wall muscles. 16.The system of claim 14, wherein: the second site is selected from thegroup consisting of the patient's: muscle fibers of the patient'spyloric sphincter and nerves to the patient's pyloric sphincter.
 17. Asystem for producing a desired effect by therapeutically activatingtissue at a first predetermined site within a patient's body and forreducing a corresponding undesired side effect by blocking activation orconduction of action potentials of tissue at a second predetermined sitewithin the patient's body, the system comprising: at least one signalgenerator capable of simultaneously producing both low frequencystimulation and high frequency stimulation or direct current pulses; andat least one implantable lead including a first electrode coupled to theat least one signal generator, the first electrode being adapted totherapeutically activate tissue at the first predetermined site byapplying low frequency stimulation, the at least one implantable leadincluding a second electrode coupled to the at least one signalgenerator, the second electrode being adapted to block activation ofelectrically excitable tissue at the second site by applying highfrequency stimulation or one or more direct current pulses or both highfrequency stimulation and one or more direct current pulses at or nearthe second site.
 18. The system of claim 17, wherein: the desired effectis peristalsis of the patient's intestine; and the undesired effect isclosure of the patient's ileocecal valve to the patient's colon.
 19. Thesystem of claim 18, wherein: the first site is selected from the groupconsisting of the patient's: intestinal wall smooth muscle, hypogastricplexus, and nerves to the patient's hypogastric plexus.
 20. The systemof claim 18, wherein: the second site is selected from the groupconsisting of the patient's: ileocecal valve, mesenteric ganglia, dorsalroot, spinal dorsal columns, and splanchnic nerves.
 21. The system ofclaim 17, wherein: the desired effect is selected from the groupconsisting of: defibrillation of the patient's atria or defibrillationof the patient's ventricles; and the undesired side effect is pain. 22.The system of claim 21, wherein: the first site is selected from thegroup consisting of: a heart pacing lead inside the patient's heartchambers and a heart pacing lead outside the patient's heart chambers.23. The system of claim 21, wherein: the second site is selected fromthe group consisting of the patient's: vagus nerve, branches of thepatient's vagus nerve from the patient's heart, thoracic sympatheticnerves, ansa subclavia, sympathetic trunk ganglia (T1-T4), stellateganglia, cervical ganglia (C1-C 8), celiac plexus, brachial plexi,dorsal roots (C1-T4), spinal dorsal columns, and dorsal roots.
 24. Thesystem of claim 17, wherein: the desired effect is extension of thepatient's leg: the first site is the patient's femoral nerve to thepatient's quadriceps femoris; the undesired side effect isco-contraction of the antagonist muscles; and the second site is thepatient's tibial nerve to the patient's gastrocnemius muscle.
 25. Thesystem of claim 17, wherein: the desired effect is movement of one ofthe patient's joints in a predetermined direction; the first site is thepatient's peripheral nerve; the undesired side effect is co-contractionof antagonist muscles; and the second site is the patient's nerve branchto an antagonist muscle.
 26. The system of claim 17, wherein: thedesired effect is activation of peripheral nerve axons to cause musclecontraction or promote organ functionality; the first site is thepatient's peripheral nerve or spinal ventral root; the undesired sideeffect is unpleasant sensation or causation of undesired reflexes; andthe second site is selected from the group consisting of the patient'sspinal dorsal roots, dorsal columns, and ventrolateral spinal cordsurface near the spinothalamic tract.
 27. The system of claim 17,wherein the high frequency stimulation or the direct current pulses orboth the high frequency stimulation and the direct current pulses beginbefore and continue during the therapeutic activation.
 28. The system ofclaim 17, wherein the high frequency stimulation or the direct currentpulses or both the high frequency stimulation and the direct currentpulses begin with a relatively low amplitude and the amplitude isgradually increased.
 29. The system of claim 17, wherein the highfrequency stimulation or the direct current pulses or both the highfrequency stimulation and the direct current pulses are terminated bygradually reducing the amplitude of the high frequency stimulation orthe direct current pulses or both the high frequency stimulation and thedirect current pulses.
 30. The system of claim 17, further comprising: asensor for sensing a state of the tissue at the second site or at a sitethat is remote from both the first site and the second site; and means,responsive to the sensor, for adjusting at least one parameter of thehigh frequency stimulation or the direct current pulses or both the highfrequency stimulation and the direct current pulses, the parameter beingselected from the group consisting of: pulse amplitude, pulse width,pulse frequency, pulse duty cycle, pulse polarity, and pulse waveform.31. The system of claim 17, further comprising: a sensor for sensing astate of the tissue at the second site or at a site that is remote fromboth the first site and the second site; and means, responsive to anindication from the sensor that tissue at the second site or at theremote site is activated, for applying the high frequency stimulation orthe direct current pulses or both the high frequency stimulation and thedirect current pulses to the second site.
 32. A system for producing adesired effect by therapeutically activating tissue at a firstpredetermined site within a patient's body and for reducing acorresponding undesired side effect by blocking activation of tissue orconduction of action potentials at a second predetermined site withinthe patient's body, the system comprising: a first signal generator forproducing low frequency stimulation; a second signal generator forproducing high frequency and/or direct current pulse stimulation; afirst implantable lead including a first electrode coupled to the firstsignal generator, the first electrode being adapted to therapeuticallyactivate tissue at the first predetermined site by applying lowfrequency stimulation; and a second implantable lead including a secondelectrode coupled to the second signal generator, the second electrodebeing adapted to block activation of electrically excitable tissue orconduction of action potentials at the second site by applying highfrequency stimulation or one or more direct current pulses or both highfrequency stimulation and one or more direct current pulses at or nearthe second site.
 33. The system of claim 32, wherein: the desired effectis promotion of micturition; and the undesired side effect is sphinctercontraction.
 34. The system of claim 33, wherein: the first site isselected from the group consisting of the patient's bladder dome, sacralroots, and pelvic plexus.
 35. The system of claim 34, wherein: thesecond site is selected from the group consisting of the patient's:sacral dorsal roots, spinal dorsal columns, conus medullaris, pudendalnerve, hypogastric plexi, and perineal nerve.
 36. The system of claim32, wherein: the desired effect is promotion of defecation; and theundesired side effect is selected from the group consisting of:sphincter contraction, elevated pelvic floor, and sharp ano-rectalangle.
 37. The system of claim 36, wherein: the first site is selectedfrom the group consisting of the patient's: hypogastric plexus, pelvicplexus, nerves to rectum, sacral roots, pelvic plexus, and rectalmuscle.
 38. The system of claim 36, wherein: the second site is selectedfrom the group consisting of the patient's: sacral dorsal roots, spinaldorsal columns, conus medullaris, pudendal nerve, and nerves to thepatient's pelvic floor muscles.
 39. The system of claim 32, wherein: thedesired effect is peristalsis of the patient's esophagus; and theundesired side effect is contraction at the patient's gastroesphagealsphincter.
 40. The system of claim 39, wherein: the first site isselected from the group consisting of the patient's: esophagus, nervesto the patient's esophagus, pharynx, and nerves to the patient'spharynx.
 41. The system of claim 39, wherein: the second site isselected from the group consisting of the patient's: hiatal esophagusarea near the patient's diaphragm and nerves to the patient's esophagus.42. The system of claim 32, wherein: the desired effect is peristalsisof the patient's ureter; and the undesired side effect is closure of thepatient's anti-reflux valves near the patient's bladder trigone.
 43. Thesystem of claim 41, wherein: the first site is selected from the groupconsisting of the patient's: renal pelvis and a portion of the patient'sureter.
 44. The system of claim 41, wherein: the second site is selectedfrom the group consisting of the patient's: base of the bladder near anentrance of the ureter, hypogastric plexus, and pelvic plexus.
 45. Thesystem of claim 32, wherein: the desired effect is peristalsis of thepatient's stomach; and the undesired effect is closure of the patient'spyloric sphincter.
 46. The system of claim 45, wherein: the first siteis selected from the group consisting of the patient's: stomach wallmuscles and nerves leading to the patient's stomach wall muscles. 47.The system of claim 45, wherein: the second site is selected from thegroup consisting of the patient's: muscle fibers of the patient'spyloric sphincter and nerves to the patient's pyloric sphincter.
 48. Asystem for producing a desired effect by therapeutically activatingtissue at a first predetermined site within a patient's body and forreducing a corresponding undesired side effect by blocking activation oftissue or conduction of action potentials at a second predetermined sitewithin the patient's body, the system comprising: at least one signalgenerator capable of simultaneously producing both high frequencystimulation and low frequency stimulation; and a first implantable leadincluding a first electrode coupled to the signal generator, the firstelectrode being adapted to therapeutically activate tissue at the firstpredetermined site by applying low frequency stimulation; and a secondimplantable lead including a second electrode coupled to the signalgenerator, the second electrode being adapted to block activation ofelectrically excitable tissue or conduction of action potentials at thesecond site by applying high frequency stimulation or one or more directcurrent pulses or both high frequency stimulation and one or more directcurrent pulses at or near the second site.
 49. The system of claim 48,wherein: the desired effect is peristalsis of the patient's intestine;and the undesired effect is closure of the patient's ileocecal valve tothe patient's colon.
 50. The system of claim 49, wherein: the first siteis selected from the group consisting of the patient's: intestinal wallsmooth muscle, hypogastric plexus, and nerves to the patient'shypogastric plexus.
 51. The system of claim 49, wherein: the second siteis selected from the group consisting of the patient's: ileocecal valve,mesenteric ganglia, dorsal root, spinal dorsal columns, and splanchnicnerves.
 52. The system of claim 48, wherein: the desired effect isselected from the group consisting of: defibrillation of the patient'satria or defibrillation of the patient's ventricles; and the undesiredside effect is pain.
 53. The system of claim 52, wherein: the first siteis selected from the group consisting of: a heart pacing lead inside thepatient's heart chambers and a heart pacing lead outside the patient'sheart chambers.
 54. The system of claim 52, wherein: the second site isselected from the group consisting of the patient's: vagus nerve,branches of the patient's vagus nerve from the patient's heart, thoracicsympathetic nerves, ansa subclavia, sympathetic trunk ganglia (T1-T4),stellate ganglia, cervical ganglia (C1-C8), celiac plexus, brachialplexi, dorsal roots (C1-T4), spinal dorsal columns, and dorsal roots.55. The system of claim 48, wherein: the desired effect is extension ofthe patient's leg: the first site is the patient's femoral nerve to thepatient's quadriceps femoris; the undesired side effect isco-contraction of the antagonist muscles; and the second site is thepatient's tibial nerve to the patient's gastrocnemius muscle.
 56. Thesystem of claim 48, wherein: the desired effect is movement of one ofthe patient's joints in a predetermined direction; the first site is thepatient's peripheral nerve; the undesired side effect is co-contractionof antagonist muscles; and the second site is the patient's nerve branchto an antagonist muscle.
 57. The system of claim 48, wherein: thedesired effect is activation of peripheral nerve axons to cause musclecontraction or promote organ functionality; the first site is thepatient's peripheral nerve or spinal ventral root; the undesired sideeffect is unpleasant sensation or causation of undesired reflexes; andthe second site is selected from the group consisting of the patient'sspinal dorsal roots, dorsal columns, and ventrolateral spinal cordsurface near the spinothalamic tract.
 58. The system of claim 48,wherein the high frequency stimulation or the direct current pulses orboth the high frequency stimulation and the direct current pulses beginbefore and continue during the therapeutic activation.
 59. The system ofclaim 48, wherein the high frequency stimulation or the direct currentpulses or both the high frequency stimulation and the direct currentpulses begin with a relatively low amplitude and the amplitude isgradually increased.
 60. The system of claim 48, wherein the highfrequency stimulation or the direct current pulses or both the highfrequency stimulation and the direct current pulses are terminated bygradually reducing the amplitude of the high frequency stimulation orthe direct current pulses or both the high frequency stimulation and thedirect current pulses.
 61. The system of claim 48, further comprising: asensor for sensing a state of the tissue at the second site or at a sitethat is remote from both the first site and the second site; and means,responsive to the sensor, for adjusting at least one parameter of thehigh frequency stimulation or the direct current pulses or both the highfrequency stimulation and the direct current pulses, the parameter beingselected from the group consisting of: pulse amplitude, pulse width,pulse frequency, pulse duty cycle, pulse polarity, and pulse waveform.62. The system of claim 48, further comprising: a sensor for sensing astate of the tissue at the second site or at a site that is remote fromboth the first site and the second site; and means, responsive to anindication from the sensor that tissue at the second site is activated,for applying the high frequency stimulation or the direct current pulsesor both the high frequency stimulation and the direct current pulses tothe second site.
 63. A method of blocking undesirable side effectactivation of electrically excitable tissue, the method comprising thesteps of: therapeutically activating tissue at a first predeterminedsite within a patient's body; and blocking activation of tissue orconduction of action potentials at a second predetermined site withinthe patient's body by applying high frequency stimulation or one or moredirect current pulses or both high frequency stimulation and one or moredirect current pulses at or near the second site.
 64. The method ofclaim 63, wherein: the desired effect is promotion of micturition; andthe undesired side effect is sphincter contraction.
 65. The method ofclaim 64, wherein: the first site is selected from the group consistingof the patient's bladder dome, sacral roots, and pelvic plexus.
 66. Themethod of claim 64, wherein: the second site is selected from the groupconsisting of the patient's: sacral dorsal roots, spinal dorsal columns,conus medullaris, pudendal nerve, hypogastric plexi, and perineal nerve.67. The method of claim 63, wherein: the desired effect is promotion ofdefecation; and the undesired side effect is selected from the groupconsisting of: sphincter contraction, elevated pelvic floor, and sharpano-rectal angle.
 68. The method of claim 67, wherein: the first site isselected from the group consisting of the patient's: hypogastric plexus,pelvic plexus, nerves to rectum, sacral roots, pelvic plexus, and rectalmuscle.
 69. The method of claim 67, wherein: the second site is selectedfrom the group consisting of the patient's: sacral dorsal roots, spinaldorsal columns, conus medullaris, pudendal nerve, and nerves to thepatient's pelvic floor muscles.
 70. The method of claim 63, wherein: thedesired effect is peristalsis of the patient's esophagus; and theundesired side effect is contraction at the patient's gastroesphagealsphincter.
 71. The method of claim 70, wherein: the first site isselected from the group consisting of the patient's: esophagus, nervesto the patient's esophagus, pharynx, and nerves to the patient'spharynx.
 72. The method of claim 70, wherein: the second site isselected from the group consisting of the patient's: hiatal esophagusarea near the patient's diaphragm and nerves to the patient's esophagus.73. The method of claim 63, wherein: the desired effect is peristalsisof the patient's ureter; and the undesired side effect is closure of thepatient's anti-reflux valves near the patient's bladder trigone.
 74. Themethod of claim 72, wherein: the first site is selected from the groupconsisting of the patient's: renal pelvis and a portion of the patient'sureter.
 75. The method of claim 72, wherein: the second site is the baseof the patient's bladder near an entrance of the ureter, hypogastricplexus, and pelvic plexus.
 76. The method of claim 63, wherein: thedesired effect is peristalsis of the patient's stomach; and theundesired effect is closure of the patient's pyloric sphincter.
 77. Themethod of claim 76, wherein: the first site is selected from the groupconsisting of the patient's: stomach wall muscles and the nerves leadingto the patient's stomach wall muscles.
 78. The method of claim 76,wherein: the second site is selected from the group consisting of thepatient's: muscle fibers of the patient's pyloric sphincter and nervesto the patient's pyloric sphincter.
 79. The method of claim 63, wherein:the desired effect is peristalsis of the patient's intestine; and theundesired effect is closure of the patient's ileocecal valve to thepatient's colon.
 80. The method of claim 79, wherein: the first site isselected from the group consisting of the patient's: intestinal wallsmooth muscle, hypogastric plexus, and nerves to the patient'shypogastric plexus.
 81. The method of claim 79, wherein: the second siteis selected from the group consisting of the patient's: ileocecal valve,mesenteric ganglia, dorsal root, spinal dorsal columns, and splanchnicnerves.
 82. The method of claim 63, wherein: the desired effect isselected from the group consisting of: defibrillation of the patient'satria or defibrillation of the patient's ventricles; and the undesiredside effect is pain.
 83. The method of claim 82, wherein: the first siteis selected from the group consisting of: a heart pacing lead inside thepatient's heart chambers and a heart pacing lead outside the patient'sheart chambers.
 84. The method of claim 82, wherein: the second site isselected from the group consisting of the patient's: vagus nerve,branches of the patient's vagus nerve from the patient's heart, thoracicsympathetic nerves, ansa subclavia, sympathetic trunk ganglia (T1-T4),stellate ganglia, cervical ganglia (C1-C8), celiac plexus, brachialplexi, dorsal roots (C1-T4), spinal dorsal columns, and dorsal roots.85. The method of claim 63, wherein: the desired effect is extension ofthe patient's leg: the first site is the patient's femoral nerve to thepatient's quadriceps femoris; the undesired side effect isco-contraction of the antagonist muscles; and the second site is thepatient's tibial nerve to the patient's gastrocnemius muscle.
 86. Themethod of claim 63, wherein: the desired effect is movement of one ofthe patient's joints in a predetermined direction; the first site is thepatient's peripheral nerve; the undesired side effect is co-contractionof antagonist muscles; and the second site is the patient's nerve branchto an antagonist muscle.
 87. The method of claim 63, wherein the highfrequency stimulation or the direct current pulses or both the highfrequency stimulation and the direct current pulses begin before andcontinue during the therapeutic activation.
 88. The method of claim 63,wherein the high frequency stimulation or the direct current pulses orboth the high frequency stimulation and the direct current pulses beginwith a relatively low amplitude and the amplitude is graduallyincreased.
 89. The method of claim 63, wherein the high frequencystimulation or the direct current pulses or both the high frequencystimulation and the direct current pulses are terminated by graduallyreducing the amplitude of the high frequency stimulation or the directcurrent pulses or both the high frequency stimulation and the directcurrent pulses.
 90. The method of claim 63, further comprising the stepsof: sensing a state of the tissue at the second site or at a site thatis remote from both the first site and the second site; and in responseto the sensing step, adjusting at least one parameter of the highfrequency stimulation or the direct current pulses or both the highfrequency stimulation and the direct current pulses, the parameter beingselected from the group consisting of: pulse amplitude, pulse width,pulse frequency, pulse duty cycle, pulse polarity, and pulse waveform.91. The method of claim 63, further comprising: sensing a state of thetissue at the second site or at a site remote from both the first siteand the second site; and in response to an indication from the sensorthat tissue at the second site is activated, applying the high frequencystimulation or the direct current pulses or both the high frequencystimulation and the direct current pulses to the second site.